Based on a working hypothesis developed earlier in the applicant's laboratory, several compounds were initially synthesized and evaluated for their antineoplastic activity. Some of these have shown inhibitory activity against a number of experimental tumor systems from the NCI screening program, the best of which is a dihydroxyaminoanthraquinone derivative, 1,4-dihydroxy-5,8-bis(((2-(2-hydroxyethyl)amino)ethyl) amino)-9,10-anthracenedione (DHAQ). The antineoplastic activity profile of DHAQ, which processes a simpler molecular structure, resembles that of Adriamycin in the preliminary study. The intent of this proposal is to conduct a search for more useful antineoplastic agents and to examine the relevance and limitations of our working hypothesis by further exploring this unique lead. Specifically, synthesis of compounds of the following classes will be studied: (1) 9,10-anthraquinones, (2) 1,4-naphthoquinones and 1,4-benzoquinones, (3) quinones related to nogalamycin, (4) xanthones, thioxanthones, and acridones, and (5) acylated polyamines containing the 2-((2-hydroxyethyl)amino)ethylamine moiety. These new compounds will be evaluated in vivo at NCI for their antineoplastic activity and in vitro at the University of Kansas Medical Center for their antiproliferative activity, cardiotoxicity, and potential mutagenicity.